1. Field of Invention
The present invention relates to the use of certain 2-amino-3-benzoylbenzeneacetic acid, salts and esters thereof in transdermal administration to animals and humans to control pain and/or inflammation.
2. Information Disclosure Statement
Certain 2-amino-3-benzoylbenzenacetic acids are disclosed in U.S. Pat. Nos. 4,045,576, 4,503,073, Great Britain Pat. No. 2,093,027, J. MED. CHEM., Vol. 25, pp 446-451 (1982) and Vol. 27, pp 1379-1388 (1984), all of which disclosures and methods of preparation disclosed therein are herein incorporated by reference. Oral, parenteral and intravenous administration of the compounds to control inflammaton and alleviate pain have been disclosed in the foregoing references. None of the above references disclose the transdermal method of administration of this invention.
Japan Kokai No. 201710/1983 published Nov. 24, 1983 discloses oral mucosal administration of Amfenac.RTM. sodium or calcium salt in a stabilized pharmaceutical paste for the treatment of inflammation of the oral cavity. Amphenac.RTM. is 2-amino-3-benzoylbenzeneacetic acid, one of the compounds useful in the present invention.
Famaey, J. B., in J. BELGE, RHUMATOL. MED. PHYS. (Belgium) Vol. 30, pp 129-141 (1975) discloses the need for studying sonophoresis in connection with creams prepared from non-steroidal anti-inflammatory drugs including Ketoprofen.RTM., among others. Ketoprofen.RTM. is 3-benzoyl-.alpha.-methylbenzeneacetic acid. The compounds of the present invention differ from Ketoprofen.RTM. in structure in that an amino group is always present in the 2-position of the primary ring.
U.S. Pat. No. 4,404,198 discloses a combination of phenylacetic acid and eugenol as a topical application to inflamed skin of animals and humans.
Remington's Pharmaceutical Sciences, 16th Ed. (1985), page 1523 states:
"Electrolytes in solution penetrate the skin poorly. Ionization of a weak electrolyte substantially reduces its permeability, e.g., sodium salicylate permeates poorly compared with salicylic acid." PA1 R.sup.2 is hydrogen, halogen, loweralkyl or loweralkoxy; PA1 R.sup.3, R.sup.4 and R.sup.5 are hydrogen or loweralkyl; PA1 X is hydrogen, halogen, loweralkyl, hydroxy, loweralkoxy, nitro, trifluoromethyl or loweralkylthio; PA1 Y is hydrogen, loweralkyl, loweralkoxy, nitro or trifluoromethyl and the hydrates thereof. The pharmaceutically acceptable salts are an alternative term to R.sup.1 being a pharmaceutically acceptable cation which includes hydrates and alcoholates thereof and of any of the acids should they occur.
In constrast to this, the salts of the 2-amino-3-benzoylbenzeneacetic acids encompassed by Formula I hereinbelow are highly potent as anti-inflammatory and analgesic agents when administered transdermally.